Multicellular tumor spheroids (MTS) can be used as in vitro systems for drug testing. The effect of polyphenols (resveratrol, baicalein, epicatechin, epigallocatechin and polyphenon 60) on cell growth, migration and adherence of spheroids from a murine mamma carcinoma cell line (4T1)was tested. Cell growth characteristics (e.g. necrosis, surface) were determined. We observed smoothing of the surface of MTS after incubation with polyphenols in contrast to the loosely packed control MTS. All examined polyphenols caused inhibition of MTS growth. The most prominent inhibitory effect was observed for baicalein and resveratrol. Furthermore, the number of proliferating cells decreased as shown by anti-Ki67 FACS analysis. We used confrontation cultures comprising of mouse embryonic stem cell-derived embryoid bodies (host)and MTS as tumor tissue to evaluate the invasion of tumor cells into the host tissue. The suppressing effect of the polyphenols on tumor cell invasion was most pronounced for cells incubated with baicalein and resveratrol. Additionally, we observed a down regulation of generation of reactive oxygen species as well as gene expression of matrix metalloproteinases which are both essential for cell invasion processes. We postulate that a possible mechanism by which polyphenols control tumor cell growth, migration and adherence might be their properties as radical scavengers.